enflurane finds a place in world anaesthesia

ENFLURANE FINDS A PLACE IN WORLD ANAESTHESIA

The volat ile anaesthetic, enflurane, may be available soon in Britain - five years after its introduction iii North America,Australasia and the rest of Europe [I]. To date there have been about 10 million administrations ofthe-drug since its first clinicaltrials in 1966; in the USA alone there have been more than 3 million safe administrations. The late introduction in Britain mayappear to be ultraconservative, but there is still some concern over the drug .

• For example, it is a potent ventilatory depressant and also has been associated with more impairment ofcardiacperformance than the other volatile anaesthetics . It has been shown to alter renal funct ion as a result of increased serumconcentrations of fluoride following hepatic defluorination of enflurane. Nephrotoxicity has been reported , and it wouldseem wise to avoid its use in patients with renal disease or renal failure . Enflurane has been shown to provoke corticalseizure activity which may be associated with clonic-tonic muscle activity.

• The cardiac depressant effects of enflurane appear to be enhanced in the presence of ~-adrenoreceptorblockers, Whilenitrous oxide seems to attenuate the drug's cardiovascular depressive action.

• On the credit side, enflurane is non-flammable, has a low blood and tissue solubility. rapid induction and recovery, and is atleast as pleasant to inhale as halothane. In fact. enflurane has taken over a sizeable proportion of the market previouslyoccupied by halothane. 'Perhaps the hesitancy of the pharmaceutical industry to introduce enflurane inBritain, and the natural conservatism of the British anaesthetist, may yet allow us the advantage ofwaiting for isoflurane to clear the chronic toxicity studies for carcinogenicity and mutagenicity, which arebeing performed at present. In the meantime, we still have a glorious opportunity to explore thealternative: supplementation of nitrous oxide with i.v . anaesthetics.

. . . It is Acceptable to Children but Has its Disadvantages TooIn several ways enflurane appears to be an ideal agent for use in the paediatric outpatient department [2]. It has a pleasant smell,the level of anaesthesia may be controlled easily. and induction and recovery from anaesthesia are significantly shorter than withhalothane. However. quite high (3-4 % ) concentrations of enllurane were required for induction in 30 children . 1-9 years old, in astudy in 150 non-selected patients undergoing a variety ofsurg ical procedures. In addition. the concentration needed to mainta insurgical anaesthesia was relatively high: 16 (53 %) of the children required 2.5 % or more and in some infants under 2 years oldcontinuous iilhalation of 5 % enflurane was inadequate. Transient muscular twitchings of the lower limbs occurred in 2 childreninhaling enflurane at over 3 % . In the 120 patients over 9 years old anaesthesia was induced with IV agents. and enflurane1.0-3.0 % seemed adequate to maintain anaesthesia .

• A feature particularly noticeable in the younger patients was an earlier need for postoperative analgesic drugs comparedwith normal practice. Consciousness returned in less than 5 minutes in 102 (68 %) of the patients when enflurane wasstopped.

• Mean arterial pressure was reduced by about 10% usually 10 minutes after the start ofanaesthesia and in half the patientsremained so 10 minutes after surgery began.

• There were no consistent changes in heart rate and rhythm. although in 12 children there were increases in heart rate butno arrhythmia following administration or adrenaline (epinephrine) .

• Respiratory depression was noted frequently and several small children became almost apnoeic shortly after induction.However. as with cardiovascular depression this was largely counteracted by the stimulus of surgery.

. . . Renal Dysfunction is Unlikely in Normal CasesConcern that enflurane might alter renal function was not borne out in 2 groups of patients with normal renal function [3]. In 10patients in whom anaesthesia was maintained with nitrous oxide in oxygen and enflurane 0.5-2 .5 %. serum inorganic fluorideincreased during anaesthesia from a control value of 5.3J.1mo1/L to a peak of 16J.1mol/L after 2 hours ofenflurane anaesthesia.and during the 4 days after the operation fell rapidly to control values. Blood enflurane rose to a mean peak of 95J.1g/rnl after 30minutes of anaesthesia. falling to less than 0.5J.1g/ml within 90 minutes ofstopping enflurane. Urinary inorganic fluoride peakedat a mean of 200j.lmo!/ day in the first 24 hours and fell to near normal by day 4. In the second group (20 patients) there were onlyminor changes in biochemical and haematological variables and no evidence of any adverse effect on liver function. Serum andurine inorganic fluoride levels were well below the potential nephrotoxic values.[I] Prys-Roberts, C.: British Journal of Anaesthesia 49: 845 (Sep 1977)[2J Black. G.W. et al.: Ibid 49: 875 (Sep \977)[3J Corall, I.M. et al.: Ibid 49: 88 1(Sep 1977)

INPHARMA 29th October, 1977 p9